Our previous study provided evidence that higher serum levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the progression of subclinical to clinically significant prostate cancer in both black and white men, especially after age 57. This paper extends the prior study by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin D (25-D), in case and control subjects. In addition, the risk of prostate cancer is related to serum levels of vitamin D-binding protein (VDBP) and total dehydroepiandrosterone and to polymorphic variation in VDBP. The expected elevated summer levels of 25-D were seen in case and control subjects and, as expected, 1,25-D did not vary throughout the year in the control subjects. Unexpectedly, lower case levels of 1,25-D were limited largely to the summer months (P = 0.01) in both black and white cases and to cases greater than or equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone and the frequencies of VDBP polymorphisms were similar in case and control subjects, although striking differences were seen in allelic frequencies in black and white men. These observations provide additional evidence that vitamin D metabolism may impact the risk of prostate cancer.